This invention relates to the field of compounds that modulate the activity of liver X receptors and their use in therapy, including the treatment of cancer.
Liver X receptors (LXRs) belong to a family of nuclear hormone receptors that are endogenously activated by cholesterol and its oxidized derivatives to mediate transcription of genes involved in maintaining glucose, cholesterol, and fatty acid metabolism. LXRα is found predominantly in the liver, with low levels found in kidney, intestine, spleen, and adrenal tissue. LXRβ is ubiquitous in mammals and was found in nearly all tissues examined. Given the intricate link between lipid metabolism and cancer cell growth, the ubiquitous expression of LXRβ in some types of cancer is unlikely to be coincidental, allowing cancer cells to synthesize lipids and lipoprotein particles to sustain their growth. At the same time, however, such stable basal expression levels make LXRβ an ideal therapeutic target